In humans, skin color arises from a complex series of cellular processes that are carried out within a group of cells known as melanocytes. Melanocytes are located in the lower part of the epidermis and their function is to synthesize a pigment, melanin, which protects the body from the damaging effects of ultraviolet radiation.
The mechanism by which skin pigmentation is formed, melanogenesis, involves the following main steps: Tyrosine→L-Dopa→Dopaquinone Dopachrome→Melanin. The first two reactions in this series are catalyzed by the enzyme, tyrosinase. The activity of tyrosinase is promoted by the action of α-melanocyte stimulating hormone and UV rays.
Typically, melanogenesis leads to a darker skin tone (i.e. a tan). However, melanogenesis can lead to undesirable pigmentation patterns as well. Examples of such undesirable pigmentation include age spots, liver spots, melasma, hyperpigmentation, etc. This has lead to research to find compounds that will inhibit melanogenesis. One of the targets of this research is tyrosinase, the enzyme which catalyses the initial steps in the generation of melanin.
U.S. Pat. No. 6,132,740 discloses a class of tyrosinase inhibitors. These compounds are 4-cycloalkyl resorcinols. One compound disclosed in the '740 patent is 4-cyclopentyl resorcinol. Example 2 of the '740 patent illustrates the preparation of 4-cyclopentyl resorcinol. The synthesis described in Example 2 can lead to the production of an oil. While this oil is a potent tyrosinase inhibitor, it may not be readily produced in the quantities required to support clinical development.
The synthesis of example 2 generates substantial quantities of various positional isomers of 4-cyclopentyl resorcinol. Examples of such isomers include 2-cyclopentyl resorcinol, 4,6-dicyclopentyl resorcinol, 2,4-dicyclopentylresorcinol, etc. It is difficult to separate the 4-cyclopentyl resorcinol from its positional isomers, especially when all of the compounds are present as oils. Thus, a need exists in the art for solid forms of 4-cyclopentyl resorcinol that may be produced more readily than the anhydrate of the prior art.